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Scientists learning to eavesdrop on the language of cells

WASHINGTON—You can't hear it or see it, but there's a mighty important conversation going on around you all the time.

This inaudible gabfest is the never-ending chatter among the trillions of cells inside each person, animal and plant. Even single-celled microbes are social beings that keep in touch with one another in order to thrive.

Thanks to recent technological advances, scientists are learning to eavesdrop on the "language" of cells and decipher their "grammar." Much is still unknown, but the research could lead to new treatments for cancer, Parkinson's, epilepsy and many other diseases.

"The language of all cellular societies is based not on sounds or gestures but on chemistry," neurobiologist Debra Niehoff wrote in her new book, "The Language of Life." Cells use "molecules where we would use words, constructing sentences from chains of proteins (to) inform, wheedle, command, exhort, reassure, nurture, criticize and instruct each other."

Cells communicate with one another by exchanging tiny chemical messengers called "transmitters" and "transporters." Familiar examples are the hormones adrenaline, dopamine, serotonin, estrogen and testosterone.

Some cells nuzzle up to one another to pass messages directly through their membranes. Others send their mail long distances through the bloodstream or lymph system. Special proteins called "receptors" wait, like doormen, on the surfaces of other cells to receive incoming signals and relay them via "second messengers" to the interior.

By decoding these transporters and receptors, doctors learn how to use drugs to intercept or moderate harmful or unpleasant messages. For example, painkillers such as aspirin and morphine work by blocking pain signals.

Biological e-mail can be a force for good or evil. You couldn't see, hear, smell, taste or feel anything without the help of these busy little molecular mail-carriers. On the other hand, miscommunication between cells "can precipitate a catastrophe," Niehoff wrote. "Such pathological misunderstandings lie at the heart of some of our most intractable diseases: cancer, diabetes, obesity, addiction, autoimmmune disorders."

For example, certain malignant tumors use a transmitter called GABA to communicate with one another and their environment as they spread to other cells, a process called metastasis.

"We may be able to evaluate drugs that affect GABA signaling to treat these aggressive types of cancers," Jeffrey Gordon, the director of the Center for Genome Sciences at Washington University in St. Louis, reported in the July 12 issue of the Proceedings of the National Academy of Sciences.

Another researcher, Eric Gouaux, a biochemist at Columbia University, recently discovered the chemical structure of a transporter that's involved in depression and other neurological disorders. He hopes his discovery will help experts design better drug treatments for these common afflictions.

"These transporters are absolutely essential for the cycle of signaling between neurons that is fundamental to brain function," Gouaux reported in the July 24 edition of the British science journal Nature. "They are the target of the widely used anti-depressants called SSRIs (selective serotonin reuptake inhibitors), including Prozac and Zoloft. Until now there has been essentially no information at the level of the atom of how this activity occurs."

Cell signals perform many useful functions besides controlling disease.

Three years ago, scientists discovered a set of light receptors in the eye, in addition to the familiar rods and cones, that determine whether it's night or day.

Russell Van Gelder, an ophthalmologist at Washington University in St. Louis, said these "photoreceptors" measured the intensity of light and passed this information through the optic nerve to so-called "clock" cells deep in the brain. The clock cells, in turn, tell you when to sleep or stay awake.

The photoreceptors are "the light meter of the eye—really a sixth sense," Van Gelder said in an e-mail message.

Another set of signals alerts so-called "natural killer cells" to an invasion by viruses, bacteria or parasites. The killer cells, which are stationed all over the body, crank up the immune system to destroy the invaders.

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"Cell communication has become one of the hottest topics in biomedical research," Niehoff said. "The number of scientific papers published on cellular communication has skyrocketed."

Despite the progress, much remains unknown about cell signaling.

For example, it isn't clear how messages "know where they're supposed to go at the time they're supposed to be there," David Featherstone, a biologist at the University of Illinois, Chicago, wrote in the July 20 Journal of Neuroscience.

If a signal is delivered to the wrong address, it can lead to a condition called "synaesthesia," where a sound may have a taste or an image may have a smell, he reported. "The molecular basis of this condition remains unknown."

Research on this problem could help doctors understand how to reconnect nerves in a spinal cord injury, Featherstone wrote.

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For more information online, go to http://en.wikipedia.org/wiki/Signal(underscore)transduction

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(c) 2005, Knight Ridder/Tribune Information Services.

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